The envelope glycoprotein of human immunodeficiency virus (HIV) plays an essential role in the initiation of HIV infection. Glycoprotein-specific antibodies neutralize viral infectivity by preventing either viral attachment, fusion, or both, and provide protection against HIV infection in vitro. Induction of glycoprotein-specific antibodies is a major strategy for the development of anti-HIV vaccines. To produce vaccines that induce antibodies capable of neutralizing the widely diverse glycoproteins present in different HIV isolates, it is essential to understand the antigenic structure of the HIV glycoprotein. Attempts to produce glycoprotein-specific mAbs have met with limited success. In this project, we are attempting to produce glycoprotein-specific mAbs using in vitro stimulation of splenocytes from primed or naive mice.